HETEROCYCLIC-ANALOGS OF DNA MINOR-GROOVE ALKYLATING-AGENTS

It is generally accepted that neoplastic transformation is related to genes alteration or oncogene activation. In particular,DNA minor groov e binding drugs have been extensively studied through the years in ord er to influence the regulation of gene expression by means of specific interactions with DNA bases moieties. Pyrrolo[2,1-c].[l,il].benzodiaz epine (PBDs), CC-1065 and distamycins are three classes of minor groov e binders which showed interesting cytotoxicity profiles, refined thro ugh already reviewed processes of SAR studies. Among the modifications to the three families of antitumor compounds, hererocyclic substituti ons have been extensively applied by many groups in order to either mo dify the reactivity profile or introduce extra interactions within the minor groove, thus changing the binding site or modulating the bindin g sequence. The updated material related to these modifications has be en rationalised and ordered in order to offer an overview of the argum ent.